Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy

Kristen R. Georgiou, Susanta K. Hui, Cory J. Xian

Research output: Contribution to journalReview article

55 Scopus citations

Abstract

The bone marrow is a complex environment that houses haematopoietic and mesenchymal cell populations and regulates bone turnover throughout life. The high proliferative capacity of these cell populations however, makes them susceptible to damage and injury, altering the steady-state of the bone marrow environment. Following cancer chemotherapy, irradiation and long-term glucocorticoid use, reduced bone and increased fat formation of marrow stromal progenitor cells results in a fatty marrow cavity, reduced bone mass and increased fracture risk. These bone and marrow defects are also observed in age-related complications such as estrogen deficiency and increased oxidative stress. Although the underlying mechanisms are yet to be clarified, recent investigations have suggested a switch in lineage commitment of bone marrow mesenchymal stem cells down the adipogenic lineage at the expense of osteogenic differentiation following such stress or injury. The Wnt/β-catenin signalling pathway is however has been recognized the key mechanism regulating stromal commitment, and its involvement in the osteogenic and adipogenic lineage commitment switch under the damaging conditions has been of great interest. This article reviews the effects of various types of stress or injury on the commitment to the adipogenic and osteogenic lineages of bone marrow stromal progenitor cells, and summarizes the roles of the Wnt/β-catenin and associated signalling pathways in the lineage commitment, switch, and recovery after damage, and as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)205-224
Number of pages20
JournalAmerican Journal of Stem Cells
Volume1
Issue number3
StatePublished - 2012

Keywords

  • Adipogenesis
  • Ageing
  • Bone marrow
  • Chemotherapy
  • Glucocorticoids
  • Mesenchymal stem cells
  • Osteogenesis
  • Oxidative stress
  • Radiotherapy
  • Wnt/β-catenin signalling

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